Voltage-independent sodium channels emerge for an expression of activity-induced spontaneous spikes in GABAergic neurons
© Lu et al.; licensee BioMed Central Ltd. 2014
Received: 10 January 2014
Accepted: 13 May 2014
Published: 20 May 2014
Cerebral overexcitation needs inhibitory neurons be functionally upregulated to rebalance excitation vs. inhibition. For example, the intensive activities of GABAergic neurons induce spontaneous spikes, i.e., activity-induced spontaneous spikes (AISS). The mechanisms underlying AISS onset remain unclear. We investigated the roles of sodium channels in AISS induction and expression at hippocampal GABAergic neurons by electrophysiological approach.
AISS expression includes additional spike capability above evoked spikes, and the full spikes in AISS comprise early phase (spikelets) and late phase, implying the emergence of new spikelet component. Compared with the late phase, the early phase is characterized as voltage-independent onset, less voltage-dependent upstroke and sensitivity to TTX. AISS expression and induction are independent of membrane potential changes. Therefore, AISS’s spikelets express based on voltage-independent sodium channels. In terms of AISS induction, the facilitation of voltage-gated sodium channel (VGSC) activation accelerates AISS onset, or vice versa.
AISS expression in GABAergic neurons is triggered by the spikelets based on the functional emergence of voltage-independent sodium channels, which is driven by intensive VGSCs’ activities.
KeywordsAction potential Spontaneous spikes Threshold potential Sodium channel Hippocampus GABAergic neurons
GABAergic neurons preserve the balance between excitation and inhibition in neuronal networks for the brain to manage well-organized cognition and behavior [1–3]. GABAergic dysfunction presumably leads to disinhibition disorders in the cerebral cortices, such as epilepsy [4–7] and psychopathy [8–11]. The upregulation of GABAergic interneurons is critical to prevent disinhibition-related brain disorders. The function of GABAergic interneurons can be upregulated at three compartments (excitatory synaptic inputs, soma and output synapses). For instance, GABAergic synapses express activity-dependent potentiation [12–15]. Excitatory synapses on GABAergic neurons are potentiated by Ca2+ signals [16–18]. The intrinsic properties of GABAergic neurons are changed in behavioral plasticity [19–21]. The persistent spikes in GABAergic neurons are induced by their repetitive activities [22, 23].
Activity-induced spontaneous spikes (AISS) at GABAergic neurons are presumably initiated at their axons and modulated by neuropeptides [22, 23]. The mechanisms essential for AISS induction and expression remain elusive. As the generation of spikes is function of sodium channels [24–29], we propose to study whether a conversion of evoked spikes into AISS results from a functional emergence of voltage-independent sodium channels and how these sodium channels work for AISS induction and expression.
To address these questions, we conducted the experiments at GABAergic neurons in hippocampal slices. Our strategies include the followings. If the intensive activities of voltage-gated sodium channels (VGSC) drive AISS induction, the facilitation of VGSC activation should shorten induction phase, or vice versa. If AISS expression is associated with a decreased threshold near resting membrane potential, AISS onset is based on the voltage-independence of sodium channels. Furthermore, the functional emergence of such voltage-independent sodium channels for AISS expression will be granted by seeing additional spike capability and two upstroke phases (such as voltage-independent and voltage-dependent sodium currents) in AISS, compared with evoked spikes.
Electrical signals were recorded at GABAergic neurons that were genetically labeled with GFP in mouse hippocampal slices under current-clamp or voltage-clamp. Depolarization pulses were repetitively injected into the neurons to induce sequential spikes. Some of these neurons were able to fire spontaneous spikes, i.e., activity-induced spontaneous spikes (AISS). We analyzed evoked spikes and AISS, in terms of their threshold potential, spike upstroke, voltage-dependence and pharmacology, in order to figure out mechanisms underlying AISS induction and expression.
Intensive activity induces spontaneous spikes in hippocampal GABAergic neurons
Spontaneous spikes can be triggered by spontaneous excitatory synaptic activities and produced based on neuronal intrinsic property. Spike threshold potential can be used as an index to indicate whether AISS onset is synaptic potential dependent or intrinsically voltage-independent. Compared with evoked spikes (blue traces in Figure 1C ~ D) and evoked spikes just before AISS onset (green), AISS waveforms (red traces) show that their threshold potentials (Vts) reduce near the resting membrane potential and their energetic barriers (ΔV;  tend to be zero. The values of Vts and ΔV gradually reduce in AISS induction (Figure 1E and 1G, n = 29). Vts is close to the resting membrane potential (red symbols in 1E) and ΔV appears zero just before AISS onset (red symbols in 1G). Therefore, AISS-expressed neurons demonstrate dynamical ΔV decrease. Zero ΔV indicates the voltage-independence of AISS expression. In addition, ΔV decreases dynamically in each evoked spikes train and recovers partially in inter-spike trains, as showed a gradual increase of ΔV coefficient variation (CV) in Figure 1H. The increase of ΔV’s CV in late phase of AISS induction further indicates that the conversion of evoked spikes into AISS expression is a spike-driven process.
In brief, AISS expression is voltage-independent and AISS induction is spike-driven. In terms of AISS expression, we focused on examining whether new voltage-independent sodium channels emerged for AISS expression. If it is a case, we expect to see the decrease of spike threshold potential near resting membrane potential, the inclusion of voltage-independent and voltage-dependent sodium currents in AISS waveforms and the addition of spike ability in AISS above evoked spikes. On the other hand, we studied whether the spike-driven process for AISS induction was based on the intensive activity of voltage-gated sodium channels (VGSC). If it is a case, manipulating VGSC’s dynamics should change the efficiency of AISS induction.
A voltage-independent component of sodium channel currents emerges for AISS expression
AISS expression includes an additional component of spikes beyond evoked spikes
We confirmed the addition of this new component by analyzing spike capability in evoked spikes train just before AISS onset versus in the first evoked spikes train. If spike frequency is higher in the train just before AISS onset than the first train by a given depolarization pulse, the new component of sodium currents is added into VGSC current for AISS expression. Spike frequency is significantly higher in the train just before AISS onset (green trace and symbols in Figure 2D ~ F) than in the first train (blue trace and symbols; an asterisk, p < 0.05; two asterisks, p < 0.01 n = 29). Thus, a new component of sodium current is added for AISS expression.
The results in Figures 1 and 2 imply an emergence of voltage-independent sodium currents for AISS expression. Moreover, if each of spike waves in AISS is separated into voltage-independent and voltage-dependent components of sodium channel currents that are different in biophysics and pharmacology, this implication will be warranted.
The full spikes in AISS include two phases
The hypothesis about adding new voltage-independent component of sodium currents into VGSC ones for AISS expression predicts that spike upstrokes in AISS should be separated into two phases that have different Vts and rising slopes. If the voltage-independent component is somehow unable to trigger voltage-dependent one, we should see the spikelet, or vice versa, such that the spikelets and spikelet-spike mixes are present in AISS. A common approach to merit rising slope and Vts for the spikes is the phase-plots of dV/dt versus membrane potentials [32, 33]. The conductance, density and activity synchrony of the sodium channels influence the rising slope of the spike upstroke [34, 35]. If more than one component is seen in the spike upstrokes, two populations of sodium channels are assumed.
Spikelets in AISS are independent of membrane potential change compared with full spikes
In summary, full spikes in AISS include two components, i.e., voltage-independent spikelets and voltage-dependent phase two spikes. These spikelets drive membrane potential depolarization toward the threshold that triggers phase two spikes in each of AISS waveforms.
The spikelets are less sensitive to TTX than full spikes
Compared with phase two, phase one (spikelets) has an onset threshold near to resting membrane potential, its generation independent of membrane potential change and the less sensitivity to TTX. Phase two in AISS and evoked spikes are similar in voltage-dependence, time-dependent recovery (Figure 4F) and TTX sensitivity (Figure 6). Therefore, the generation of the spikelets is based on the newly emerged component of sodium channels that are voltage-independent for AISS expression, but phase two of AISS is controlled by VGSCs.
AISS induction is not influenced by membrane potentials
The activity state of voltage-gated sodium channels influences AISS induction
In terms of AISS induction, we focused on examining a role of voltage-gated ion channels based on the following facts. AISS was induced by membrane depolarization without synaptic stimulation in the GABAergic neurons. AISS induction was a spike-driven process. Because of the influence of potassium channels on sequential spikes, a role of voltage-gated potassium channel in AISS induction was examined by applying tetraethylammonium (TEA). AISS was induced in the presence of 40 mM TEA (Additional file 3: Figure S3), in which the blockade of potassium channels was demonstrated by an incomplete repolarization (arrow). Because of the low threshold for T-type calcium channels, similar to AISS onset, a role of T-type calcium channel in AISS induction was examined by using its inhibitor mibefradil. AISS was induced in the presence of 100 μM mibefradil (Additional file 4: Figure S4). Such results indicate that the activity state of VGSCs may be involved in the spike-driven process for AISS induction.
To examine a role of VGSCs in AISS induction, we observed whether the upregulation of VGSC dynamics accelerated AISS induction or the downregulation of VGSC dynamics postponed its induction. VGSC dynamics was upregulated by using ATX-II (a blocker of VGSC inactivation; [35, 36] or hyperpolarization , but was downregulated by using anandamide . In the following experiments, we induced AISS in control ACSF. After AISS disappeared for six minutes, we re-induced AISS in one of these pharmacological reagents or hyperpolarization, a protocol similar to Additional file 1: Figure S1.
Intensive activity in hippocampal GABAergic neurons induces spontaneous spikes (Figure 1). An onset of the activity-induced spontaneous spike (AISS) is accelerated by VGSC activation and delayed by VGSC inactivation (Figures 8, 9 and 10). AISS induction is a spike-driven process based on intensive activities of VGSC. After AISS expression, the upstrokes of full spikes in AISS are separated into a newly emerged voltage-independent component of sodium currents in early phase (i.e., spikelet) and a voltage-dependent component in late phase (Figures 2, 3 and 4). This early phase is featured as a zero threshold potential and TTX sensitivity in its expression and voltage-independence in its induction (Figures 3, 4, 5, 6 and 7). AISS production is based on the functional emergence of voltage-independent sodium channels in neuronal processes driven by intensive VGSC-mediated spiking.
In terms of the physiological impact of AISS expression in GABAergic neurons, AISS onset may be self-compensation processes in their networks and individual neurons. Intensive activities in inhibitory neurons hint an over-excited state of their local network. AISS onset helps to suppress this overexcitation in these network neurons. Moreover, once AISS onset at a GABAergic neuron, an emergence of voltage-independent sodium channels is associated with an attenuation of VGSC’s activity (Figures 2, 3, and 4). These functionally attenuated VGSCs can still be activated by the spikelets mediated by newly emerged voltage-independent sodium channels. A mutual substitution in the functions of VGSCs and voltage-independent sodium channels is a basis that AISS’s onset compensates the weakness of evoked spikes (Figure 2D ~ E). These facts grant a notion that the neural homeostasis is maintained among subcellular compartments and network neurons .
The induction of AISS at GABAergic neurons is a spike-driven process that the sufficient amount of evoked spikes is needed (Figure 1; also see [22, 23]). Compared to the control, a facilitation of VGSC activation reduces the number of spikes needed for AISS induction (Figure 8 and 9), and an attenuation of VGSC activities requires more spikes for AISS induction (Figure 10). Therefore, the functional states of VGSCs control AISS induction. The processes underlying VGSC-driven AISS onset remain elusive. Previous studies show that the gap junctions and neuropeptides modulate AISS induction [22, 23]. How the multiple processes coordinately regulate AISS induction needs to be addressed. It is noteworthy that the voltage-dependent potassium channels may not be required for AISS induction (Additional file 3: Figure S3), however, they may be involved AISS expression since the shape of AISS repolarization changes (Figure 1C ~ D), which will be examined in our future study.
In the analysis of AISS waveforms by phase-plot, two phases are distinguished in their upstrokes based on biophysical and pharmacological properties. AISS’s early phase shows zero threshold potential, faster upstroke, voltage-independence and less TTX-sensitivity, compared with its late phase (Figures 3, 4, 5 and 6). This early phase triggers the late phase. The features of the early phase (spikelets) indicate the functional emergence of voltage-independent sodium channels for the AISS expression, which are functionally silent when hippocampal GABAergic neurons are not quite active. It remains to be investigated the mechanisms underlying the turning-on of voltage-independent sodium channels through their structural changes and/or intracellular molecular modulation.
The location of AISS onset was presumably axonal in origin because AISS was induced under the condition of axonal stimuli and somatic hyperpolarization . In our study, AISS can be induced when membrane potentials are hyperpolarized (Figure 7). The expression of AISS’s early phase (spikelets) are not influenced by the hyperpolarization (Figures 5, 6 and 7). A suggestion of axonal origin for the onset of AISS spikelets is strengthened. As AISS’s late phase is influenced by membrane potential, i.e., somatic in origin, the axonal spikelets need to be propagated to the somata to trigger the second phase of individual spikes in AISS. In these regards, the emergence of voltage-independent sodium channels for AISS expression may not be converted from the functional upregulation of somatic VGSCs, but is likely from the turn-on of axonal voltage-independent sodium channels that are silent in inactive neurons.
In terms of the molecular events from the intensive activation of somatic VGSCs to the functional emergence of axonal voltage-independent sodium channels for AISS onset, our study by calcium imaging shows the rise of intracellular Ca2+ levels during AISS induction (Additional file 5: Figure S5, n = 3). However, the preloading of 1 mM BAPTA intracellularly by the recording pipettes does not prevent AISS induction and expression (Additional file 5: Figure S5, n = 3). A rise of intracellular Ca2+ level is not required for triggering an emergence of voltage-independent sodium channels to induce AISS expression. Since AISS is a spike-driven process, other ions related to fire intensive spikes should be considered to be the triggers for AISS induction. Moreover, the persistent time from AISS onset to disappearance is often less than one minute (Figure 1, 2 and 3), this short-term reversible process may present either the clearance of intracellular accumulated ions or the dynamic activation-to-inactivation of certain enzymes during AISS expression. In terms of ions and enzymes, our testable hypothesis is that sodium and its regulated proteins are responsible for turning on silent voltage-independent sodium channels.
One could question why the increase of intracellular Ca2+ is not required for AISS induction. We interpret that an increased Ca2+ activates protein kinases, such as PKC and CaM-KII, which downregulate VGSCs’ activity [16, 39–43]. This downregulation of VGSC functions during AISS expression leads to the decrease of VGSC-dependent late phase (Figure 4). Another issue is that the results about AISS production are different from lowering intracellular Ca2+ level by BAPTA (Additional file 5: Figure S5) and manipulating extracellular Ca2+ concentration . Our interpretations to this question are given below. The extracellular Ca2+ may affect entire neural networks including excitatory and inhibitory neurons, and in turn multiple neurons influence GABAergic neurons expressing AISS. Moreover, intracellular Ca2+ level is influenced by calcium entrance from extracellular space and calcium release from intracellular stores, i.e., cytoplasm Ca2+ is not solely from extracellular space. In other words, the results from manipulating intracellular Ca2+ and altering extracellular Ca2+ level are not comparable.
Methods and materials
Procedures for cutting brain slices and doing electrophysiological experiments were approved by the Institutional Animal Care and Use Committee in the Administration Office of Laboratory Animals in Beijing China (B10831). Hippocampal slices (300 μm) were prepared from C57(GAD67-GFP) mice whose GABAergic neurons were genetically labeled by the green fluorescent protein (gifted by Dr. Yuchio Yanagawa, Gunma University Graduate School of Medicine, Japan; [44–46]. Mice in postnatal days 18–22 were anesthetized by injecting chloral hydrate (300 mg/kg) and decapitated by a guillotine. The slices were sectioned with Vibratome in the oxygenized (95% O2/5% CO2) artificial cerebrospinal fluid (mM: 124 NaCl, 3 KCl, 1.2 NaH2PO4, 26 NaHCO3, 0.5 CaCl2, 5 MgSO4, 10 dextrose and 5 HEPES; pH 7.35) at 4°C, and subsequently were held in normal oxygenated ACSF (mM: 124 NaCl, 3 KCl, 1.2 NaH2PO4, 26 NaHCO3, 2.4 CaCl2, 1.3 MgSO4, 10 dextrose and 5 HEPES; pH 7.35) 24°C for 1 ~ 2 hours before the experiments. A slice was placed to a submersion chamber (Warner RC-26G) that was perfused by the normal ACSF at 31°C for whole-cell recordings [10, 20, 47–50].
Electrophysiological study in hippocampal GABAergic neurons
A selection of hippocampal GABAergic neurons for whole-cell recording was based on the following criteria. These neurons in CA1 area of hippocampal stratum radiatum appeared smaller round soma and multiple processes, compared to relatively larger pyramidal neurons in pyramidale, under the DIC microscope (Nikon, FN-E600). These neurons labeled by GFP were identified under fluorescent microscope (Nikon, FN-E600). They fired fast sequential spikes with less adaptation in amplitudes and frequency, typical properties for the interneurons [1–3, 51–55].
These interneurons were recorded by an amplifier (MultiClapm-700B, Axon Instrument Inc, CA USA) under whole-cell current-clamp and voltage-clamp. Electrical signals were inputted into pClamp-10 (Axon Instrument Inc) with a sampling rate at 20 kHz. Transient capacitance was compensated and output bandwidth was 3 kHz. Pipette solution for recording action potentials included (mM) 150 K-gluconate, 5 NaCl, 0.4 EGTA, 4 Mg-ATP, 0.5 Tris- GTP, 4 Na-phosphocreatine and 5 HEPES (pH 7.4 adjusted by 2 M KOH). The osmolarity of pipette solution made freshly was 295–305 mOsmol. The pipette resistance was 8 ~ 10 MΩ.
The action potentials were recorded under the conditions of the current-clamp and voltage-clamp. Activity-induced spontaneous spikes (AISS) were driven by injecting depolarization pulses (200 pA and 3 seconds) in a pattern of direct current (DC) with inter-pulse intervals in 7 seconds. The strength of these depolarization pulses was sufficient to evoke the sequential spikes. The periods of injecting depolarization pulses were given until seeing AISS. The period of AISS expression lasted for a range of 10 ~ 30 seconds. After AISS disappeared for 6 minutes, we re-injected these depolarization pulses to induce AISS in each GABAergic neuron under the conditions of DC, DC plus pharmacological reagents and cosine wave. The protocols were used to examine the effects of different manipulations on the efficiency of AISS induction.
The spikes including the evoked and spontaneous ones in our study were analyzed in terms of the threshold potential (membrane potential for spike onset, abbreviation as Vts; Figure 1C), energetic barrier (a difference between threshold potential and resting membrane potential, abbreviation as ΔV;  and Figure 1C), spike frequency (Figure 2), spike phase-plot (spike dV/dt vs. membrane potential, Figure 3), input–output (current input versus spike output in Figure 2A ~ C) and spike voltage-dependence (spikes versus membrane holding potentials in Figures 5 and 7).
Spike threshold potentials and ΔV can be used to evaluate whether the spikes are easily induced and to denote how voltage-gated sodium channels (VGSC) are activated [16, 26, 31, 34, 37, 56]. After AISS onset, the spikes are separated into two phases in GABAergic neurons (Figures 2 and 3). The threshold potential for the spikelets is a membrane potential for their onset, and the threshold potential for subsequent spikes is a membrane potential for the onset of the second phase spikes (Figure 4). As the dV/dt values of spike’s rising phases reflect the efficiencies of individual VGSC activation and of multiple VGSCs’ activation [57, 58], the positive dV/dt values in spike phase-plots indicate the efficiency of synchronous activation in a population of VGSCs. The spike frequency and input–output curve will indicate the neuronal ability to convert input signals into digital spikes as well as the addition of new components into spike rising phase [26, 47]. Spontaneous spikes versus membrane holding potentials are used to test whether membrane potentials affect the induction and expression of AISS as well as the onset of AISS phases. These analyses were done under the conditions of DC (control) and various manipulations (biophysics and pharmacology), so that we are able to identify whether the functional states of sodium currents are associated with the onset of AISS.
The evoking of sequential spikes by DC and cosine waves was based on a fact that the waves to drive spike generation in vivo were classified as steady-state and fluctuated formats [35, 47], in which the cosine waveforms presumably allowed VGSCs’ recovery from previous inactivation. In the analyses of input–output curves , the depolarization pulses (1 second) in various intensities were injected into the interneurons to induce sequential spikes before and after AISS onsets. This analysis indicates the ability of these interneurons to convert excitatory inputs into spikes and the probability of VGSCs’ activation by excitatory inputs i.e., neuronal sensitivity to the excitatory inputs [16, 31, 34, 56].
It is noteworthy that we measure upstroke velocity in two phases of AISS’s spikes, respectively, instead of other properties, such as spike durations at half-height and spike amplitudes. dV/dt values well represent VGSCs’ efficiency in their synchronous activation . However, as two rising phases of AISS spikes are present, the spike duration at half-height includes the mixture of the two components, i.e., this parameter is influenced by two separate mechanisms. Moreover, spike amplitudes are affected by VGSCs and electrochemical gradients. In these regards, spike duration and amplitude may not be optimal to characterize the mechanisms of voltage-dependent and voltage-independent VGSCs in AISS onset.
The data were analyzed if the recorded neurons had resting membrane potentials negatively more than −60 mV and action potentials above 90 mV. The criteria for the acceptation of each experiment also included less than 5% changes in resting membrane potential, spike magnitudes, input and seal resistances throughout each experiment. The values for all parameters are presented as mean ± SE. The comparisons among groups are done in one way ANOVA, and before versus after treatment are done with paired t-test .
This study is supported by the National Basic Research Program (2013CB531304, 2011CB504405) and Natural Science Foundation China (30990261, 81171033) to JHW.
- Freund TF, Buzsaki G: Interneurons of the hippocampus. Hippocampus. 1996, 6: 347-470.PubMedView ArticleGoogle Scholar
- Klausberger T, Somogyi P: Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science. 2008, 321: 53-57. 10.1126/science.1149381.PubMedPubMed CentralView ArticleGoogle Scholar
- Somogyi P, Klausberger T: Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol (London). 2005, 562: 9-29. 10.1113/jphysiol.2004.078915.View ArticleGoogle Scholar
- Huguenard JR: Neuronal circuitry of thalamocortical epilepsy and mechanisms of antiabsence drug action. Adv Neurol. 1999, 79: 991-999.PubMedGoogle Scholar
- Lee J, Woo J, Favorov OV, Tommerdahl M, Lee CJ, Whitsel BL: Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons. Mol Brain. 2012, 5: 33-10.1186/1756-6606-5-33.PubMedPubMed CentralView ArticleGoogle Scholar
- McCormick DA, Contreras D: On the cellular and network bases of epileptic seizures. Annu Rev Physiol. 2001, 63: 815-846. 10.1146/annurev.physiol.63.1.815.PubMedView ArticleGoogle Scholar
- Prince DA: Epileptogenic neurons and circuits. Adv Neurol. 1999, 79: 665-684.PubMedGoogle Scholar
- Benes FM, Berretta S: GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology. 2001, 25: 1-27. 10.1016/S0893-133X(01)00225-1.PubMedView ArticleGoogle Scholar
- Maciag D, Hughes J, O’Dwyer G, Pride Y, Stockmeier CA, Sanacora G, Rajkowska G: Reduced density of calbindin immunoreactive GABAergic neurons in the occipital cortex in major depression: relevance to neuroimaging studies. Biol Psychiatry. 2010, 67: 465-470. 10.1016/j.biopsych.2009.10.027.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhang F, Liu B, Lei Z, Wang J: mGluR1,5 activation improves network asynchrony and GABAergic synapse attenuation in the amygdala: implication for anxiety-like behavior in DBA/2 mice. Mol Brain. 2012, 5: 20-10.1186/1756-6606-5-20.PubMedPubMed CentralView ArticleGoogle Scholar
- Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, Knable MB: Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry. 2005, 57: 252-260. 10.1016/j.biopsych.2004.10.019.PubMedView ArticleGoogle Scholar
- Caillard O, Ben-Ariand Y, Gaiarsa J-L: Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. J Physiol (London). 1999, 518: 109-119. 10.1111/j.1469-7793.1999.0109r.x.View ArticleGoogle Scholar
- Houston CM, He Q, Smart TG: CaMKII phosphorylation of the GABA(A) receptor: receptor subtype- and synapse-specific modulation. J Physiol. 2009, 587: 2115-2125. 10.1113/jphysiol.2009.171603.PubMedPubMed CentralView ArticleGoogle Scholar
- Poisbeau P, Cheney MC, Browning MD, Mody I: Modulation of synaptic GABAA receptor function by PKA and PKC in adult hippocampal neurons. J Neurosci. 1999, 19: 674-683.PubMedGoogle Scholar
- Wei J, Zhang M, Zhu Y, Wang JH: Ca2 + −calmodulin signalling pathway upregulates GABA synaptic transmission through cytoskeleton-mediated mechanisms. Neuroscience. 2004, 127: 637-647. 10.1016/j.neuroscience.2004.05.056.PubMedView ArticleGoogle Scholar
- Chen N, Chen X, Wang J-H: Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding. J Cell Sci. 2008, 121: 2961-2971. 10.1242/jcs.022368.PubMedView ArticleGoogle Scholar
- Lamsa KP, Heeroma JH, Somogyi P, Rusakov DA, Kullmann DM: Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit. Science. 2007, 315: 1262-1266. 10.1126/science.1137450.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang J-H, Kelly PT: Ca2+/CaM signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal fast-spiking neurons of hippocampal CA1. J Physiol (London). 2001, 533: 407-422. 10.1111/j.1469-7793.2001.0407a.x.View ArticleGoogle Scholar
- Letzkus JJ, Wolff SB, Meyer EM, Tovote P, Courtin J, Herry C, Luthi A: A disinhibitory microcircuit for associative fear learning in the auditory cortex. Nature. 2012, 480: 331-335.View ArticleGoogle Scholar
- Ni H, Huang L, Chen N, Zhang F, Liu D, Ge M, Guan S, Zhu Y, Wang JH: Upregulation of barrel GABAergic neurons is associated with cross-modal plasticity in olfactory deficit. PLoS One. 2010, 5: e13736-10.1371/journal.pone.0013736.PubMedPubMed CentralView ArticleGoogle Scholar
- Ye B, Huang L, Gao Z, Chen P, Ni H, Guan S, Zhu Y, Wang JH: The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs. PLoS One. 2012, 7: e41986-10.1371/journal.pone.0041986.PubMedPubMed CentralView ArticleGoogle Scholar
- Krook-Magnuson E, Luu L, Lee SH, Varga C, Soltesz I: Ivy and neurogliaform interneurons are a major target of mu-opioid receptor modulation. J Neurosci. 2011, 31: 14861-14870. 10.1523/JNEUROSCI.2269-11.2011.PubMedPubMed CentralView ArticleGoogle Scholar
- Sheffield ME, Best TK, Mensh BD, Kath WL, Spruston N: Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. Nat Neurosci. 2011, 14: 200-207. 10.1038/nn.2728.PubMedPubMed CentralView ArticleGoogle Scholar
- Aldrich RW, Corey DP, Stevens CF: A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 1983, 306: 436-441. 10.1038/306436a0.PubMedView ArticleGoogle Scholar
- Khaliq ZM, Bean BP: Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances. J Neurosci. 2010, 30: 7401-7413. 10.1523/JNEUROSCI.0143-10.2010.PubMedPubMed CentralView ArticleGoogle Scholar
- Chen N, Zhu Y, Gao X, Guan S, Wang J-H: Sodium channel-mediated intrinsic mechanisms underlying the differences of spike programming among GABAergic neurons. Biochem Biophys Res Commun. 2006, 346: 281-287. 10.1016/j.bbrc.2006.05.120.PubMedView ArticleGoogle Scholar
- Goldman L: Stationarity of sodium channel gating kinetics in excised patches from neuroblastoma N1E 115. Biophys J. 1995, 69: 2364-2368. 10.1016/S0006-3495(95)80105-0.PubMedPubMed CentralView ArticleGoogle Scholar
- Hodgkin AL, Huxley AF: Propagation of electrical signals along giant nerve fibers. Proc R Soc Lond B Biol Sci. 1952, 140: 177-183. 10.1098/rspb.1952.0054.PubMedView ArticleGoogle Scholar
- Huxley AF, Stampfli R: Evidence for saltatory conduction in peripheral myelinated nerve fibres. J Physiol. 1949, 108: 315-339.PubMed CentralView ArticleGoogle Scholar
- Sheffield ME, Edgerton GB, Heuermann RJ, Deemyad T, Mensh BD, Spruston N: Mechanisms of retroaxonal barrage firing in hippocampal interneurons. J Physiol. 2013, 591: 4793-4805. 10.1113/jphysiol.2013.258418.PubMedPubMed CentralView ArticleGoogle Scholar
- Ge R, Chen N, Wang JH: Real-time neuronal homeostasis by coordinating VGSC intrinsic properties. Biochem Biophys Res Commun. 2009, 387: 585-589. 10.1016/j.bbrc.2009.07.066.PubMedView ArticleGoogle Scholar
- McCormick DA, Shu Y, Yu Y: Neurophysiology: Hodgkin and Huxley model–still standing?. Nature. 2007, 445: E1-E2. 10.1038/nature05523. discussion E2-3PubMedView ArticleGoogle Scholar
- Naundorf B, Wolf F, Volgushev M: Unique features of action potential initiation in cortical neurons. Nature. 2006, 440: 1060-1063. 10.1038/nature04610.PubMedView ArticleGoogle Scholar
- Chen N, Yu J, Qian H, Ge R, Wang JH: Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical pyramidal neurons. PLoS One. 2010, 5 (7): e11868-10.1371/journal.pone.0011868.PubMedPubMed CentralView ArticleGoogle Scholar
- Ge R, Qian H, Chen N, Wang JH: Input-dependent subcellular localization of spike initiation between soma and axon at cortical pyramidal neurons. Mol Brain. 2014, 7: 26-10.1186/1756-6606-7-26.PubMedPubMed CentralView ArticleGoogle Scholar
- Rathmayer W: Anemone toxin discriminates between ionic channels for receptor potential and for action potential production in a sensory neuron. Neurosci Lett. 1979, 13: 313-318. 10.1016/0304-3940(79)91512-X.PubMedView ArticleGoogle Scholar
- Chen N, Chen X, Yu J, Wang J-H: After-hyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels. Biochem Biophys Res Commun. 2006, 346: 938-945. 10.1016/j.bbrc.2006.06.003.PubMedView ArticleGoogle Scholar
- Theile JW, Cummins TR: Inhibition of Navbeta4 peptide-mediated resurgent sodium currents in Nav1.7 channels by carbamazepine, riluzole, and anandamide. Mol Pharmacol. 2011, 80: 724-734. 10.1124/mol.111.072751.PubMedPubMed CentralView ArticleGoogle Scholar
- Ashpole NM, Herren AW, Ginsburg KS, Brogan JD, Johnson DE, Cummins TR, Bers DM, Hudmon A: Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol Chem. 2012, 287: 19856-19869. 10.1074/jbc.M111.322537.PubMedPubMed CentralView ArticleGoogle Scholar
- Hourez R, Azdad K, Vanwalleghem G, Roussel C, Gall D, Schiffmann SN: Activation of protein kinase C and inositol 1,4,5-triphosphate receptors antagonistically modulate voltage-gated sodium channels in striatal neurons. Brain Res. 2005, 1059: 189-196. 10.1016/j.brainres.2005.08.031.PubMedView ArticleGoogle Scholar
- Kato K, Iwamoto T, Kida S: Interactions between alphaCaMKII and calmodulin in living cells: conformational changes arising from CaM-dependent and -independent relationships. Mol Brain. 2013, 6: 37-10.1186/1756-6606-6-37.PubMedPubMed CentralView ArticleGoogle Scholar
- Sanhueza M, Lisman J: The CaMKII/NMDAR complex as a molecular memory. Mol Brain. 2013, 6: 10-10.1186/1756-6606-6-10.PubMedPubMed CentralView ArticleGoogle Scholar
- Vijayaragavan K, Boutjdir M, Chahine M: Modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by protein kinase A and protein kinase C. J Neurophysiol. 2004, 91: 1556-1569. 10.1152/jn.00676.2003.PubMedView ArticleGoogle Scholar
- Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T: Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol. 2003, 467: 60-79. 10.1002/cne.10905.PubMedView ArticleGoogle Scholar
- Ohira K, Takeuchi R, Iwanaga T, Miyakawa T: Chronic fluoxetine treatment reduces parvalbumin expression and perineuronal nets in gamma-aminobutyric acidergic interneurons of the frontal cortex in adult mice. Mol Brain. 2013, 6: 43-10.1186/1756-6606-6-43.PubMedPubMed CentralView ArticleGoogle Scholar
- Ono M, Yanagawa Y, Koyano K: GABAergic neurons in inferior colliculus of the GAD67-GFP knock-in mouse: electrophysiological and morphological properties. Neurosci Res. 2005, 51: 475-492. 10.1016/j.neures.2004.12.019.PubMedView ArticleGoogle Scholar
- Ge R, Qian H, Wang JH: Physiological synaptic signals initiate sequential spikes at soma of cortical pyramidal neurons. Mol Brain. 2011, 4: 19-10.1186/1756-6606-4-19.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang J-H: Short-term cerebral ischemia causes the dysfunction of interneurons and more excitation of pyramidal neurons. Brain Res Bull. 2003, 60: 53-58. 10.1016/S0361-9230(03)00026-1.PubMedView ArticleGoogle Scholar
- Yu J, Qian H, Chen N, Wang JH: Quantal glutamate release is essential for reliable neuronal encodings in cerebral networks. PLoS One. 2011, 6: e25219-10.1371/journal.pone.0025219.PubMedPubMed CentralView ArticleGoogle Scholar
- Yu J, Qian H, Wang JH: Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes. Mol Brain. 2012, 5: 26-10.1186/1756-6606-5-26.PubMedPubMed CentralView ArticleGoogle Scholar
- Maccaferri G, Lacaille JC: Interneuron Diversity series: Hippocampal interneuron classifications–making things as simple as possible, not simpler. Trends Neurosci. 2003, 26: 564-571. 10.1016/j.tins.2003.08.002.PubMedView ArticleGoogle Scholar
- McKay BE, Turner RW: Physiological and morphological development of the rat cerebellar Purkinje cell. J Physiol (London). 2005, 567 (Pt3): 829-850.View ArticleGoogle Scholar
- Wang JH, Wei J, Chen X, Yu J, Chen N, Shi J: The gain and fidelity of transmission patterns at cortical excitatory unitary synapses improve spike encoding. J Cell Sci. 2008, 121: 2951-2960. 10.1242/jcs.025684.PubMedView ArticleGoogle Scholar
- Wehr M, Zador AM: Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature. 2003, 426: 442-446. 10.1038/nature02116.PubMedView ArticleGoogle Scholar
- Yang Z, Wang JH: Frequency-Dependent Reliability of Spike Propagation Is Function of Axonal Voltage-Gated Sodium Channels in Cerebellar Purkinje Cells. Cerebellum. 2013, 12 (6): 862-869. 10.1007/s12311-013-0499-2.PubMedView ArticleGoogle Scholar
- Chen N, Chen SL, Wu YL, Wang JH: The refractory periods and threshold potentials of sequential spikes measured by whole-cell recordings. Biochem Biophys Res Commun. 2006, 340: 151-157. 10.1016/j.bbrc.2005.11.170.PubMedView ArticleGoogle Scholar
- Berecki G, Wilders R, de Jonge B, van Ginneken AC, Verkerk AO: Re-evaluation of the action potential upstroke velocity as a measure of the Na + current in cardiac myocytes at physiological conditions. PLoS One. 2010, 5: e15772-10.1371/journal.pone.0015772.PubMedPubMed CentralView ArticleGoogle Scholar
- Remme CA, Verkerk AO, Nuyens D, van Ginneken AC, van Brunschot S, Belterman CN, Wilders R, van Roon MA, Tan HL, Wilde AA, Carmeliet P, de Bakker JM, Veldkamp MW, Bezzina CR: Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation. 2006, 114: 2584-2594. 10.1161/CIRCULATIONAHA.106.653949.PubMedView ArticleGoogle Scholar
- Yang Z, Gu E, Lu X, Wang JH: Essential role of axonal VGSC inactivation in time-dependent deceleration and unreliability of spike propagation at cerebellar Purkinje cells. Mol Brain. 2014, 7: 1-10.1186/1756-6606-7-1.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhao J, Wang D, Wang JH: Barrel cortical neurons and astrocytes coordinately respond to an increased whisker stimulus frequency. Mol Brain. 2012, 5: 12-10.1186/1756-6606-5-12.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.